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Biomedical subjects

P Vasseur

Publications and source records attributed to P Vasseur.

At least 19 recordsLinked to original sources
PubMed2006

Toxicity of nonylphenol on the cnidarian Hydra attenuata and environmental risk assessment.

Alkylphenols and their derivatives, alkylphenol polyethoxylates (APEs), are synthetic chemicals of concern owing to their endocrine properties. Nonylphenol (NP) is a critical APE metabolite because of its recalcitrance to biodegradation, toxicity, and ability to bio-accumulate in aquatic organisms. Studies of NP effects in vertebrates demonstrated estrogenic disrupting properties in fish, birds, reptiles, and mammal cells in which NP displaces the natural estrogen from its receptor. Less is known on its toxicity toward invertebrates. Effects on reproduction have been reported, but toxicity on development has been poorly documented thus far. We investigated NP toxicity on survival and regeneration of the freshwater coelenterate Hydra attenuata. Hydra is known for its regenerative capacity and its sensitivity to chemical pollution. It has been used for over 20 years to screen for teratogenicity of chemicals (Johnson et al. (1982) Teratog Carcinog Mutagen 2:263-276). Our results showed that hydra appeared as one of the most sensitive species to acute and chronic toxicity of NP compared to several freshwater invertebrates. Regeneration was disrupted at NP concentrations lower than those affecting survival. Toxicity thresholds of NP for aquatic vertebrates and invertebrates are also reported and discussed in the context of environmental risk assessment and of water quality objectives recommended for surface waters in industrialized countries. NP levels have decreased during the last decade because of a voluntary agreement of surfactant producers and users. At present, concentrations of NP found in surface waters are far below 1 microg/L in Europe, but can reach several microg/L when wastewater treatment plant inefficiency occurs.

Animals↗
PubMed2006

Artificial streams in the assessment of environmental hazard of chemicals.

Artificial streams are dynamic mesocosms, simulating aquatic systems and rivers. They are useful to study ecotoxicity of chemicals and their effects on flora and fauna colonizing the streams or introduced into the channels. These artificial rivers can also be used to study the influence of ecological and hydrodynamic parameters, such as the kind of substrate of river and flow rate. Responses of the bivalve Unio tumidus to substrate type (silt, sand, and pebbles) and water flow rate (high and low) were investigated after 15 and 35 days in the channels, in order to optimize the experimental conditions for ecotoxicity study with methyl methacrylate (MMA). The toxicological effects of different concentrations of MMA on bivalves and on communities of invertebrates and diatoms were determined after several weeks of exposure at a high flow rate. Biomarkers responses measured in the digestive gland and the gills of U. tumidus were the activities of detoxification systems as early indicators of toxicity and lipid peroxidation as a marker of cytotoxicity. Effects of MMA resulted in a decrease in antioxidant activities. Disturbances in bivalves appeared at lower concentrations than in communities. This indicates sensitivity of the biomarkers studied, which are predictive indicators of ecotoxicity.

Animals↗
PubMed2005

Di-(2-ethylhexyl)phthalate (DEHP) increases Bcl-2/Bax ratio and modifies c-myc expression in Syrian hamster embryo (SHE) cells.

The objective of this work was to study the anti-apoptotic properties of the non-genotoxic rodent carcinogen, di(2-ethylhexyl)phthalate (DEHP) in Syrian hamster embryo (SHE) cells. We demonstrated that a 24 h pre-treatment of SHE cells with 50 microM DEHP inhibited apoptosis triggered by growth factors deprivation. The RNA expression levels of the regulator genes involved in the apoptotic pathway, bcl-2, bax and of c-myc were measured using Western blotting and RT-PCR. We showed that a 24 h treatment of SHE cells with 50 microM DEHP increased (P < 0.05) the bcl-2 expression, while c-myc expression was decreased. No effect on bax expression was observed in the range of 10-50 microM. The defective regulation of apoptosis caused by DEHP treatment could contribute to its carcinogenicity.

Animals↗
PubMed2005

The INSERM expert review on glycol ethers: findings and recommendations.

The use of glycol ethers and their effects on health have recently attracted the attention of the French health authorities. At their request, INSERM, the French Institute of Health and Medical Research, conducted a collective expertise review on glycol ethers in 1999. INSERM Expertise Reviews are independent procedures performed by experts from several disciplines, to guarantee the objectivity and the relevance of the report. During several work sessions, the experts carried out a critical analysis of and reviewed studies concerning the toxicity of glycol ethers. This process resulted in a series of recommendations and conclusions. All these data have been published in the form of a report and have been used to help the public authorities to make decisions on how to prevent risks for professionals and consumers.

Animals↗
PubMed2004

Changes in expression of bcl-2 and bax in Syrian hamster embryo (SHE) cells exposed to ZnCl2.

Zinc is involved in many physiological processes and plays a critical role in functional and structural cells. Zinc at concentrations ranging from 100 to 150 micromol L(-1) has been shown to induce morphological transformation of Syrian hamster embryo (SHE) cells. At these concentrations, zinc inhibited apoptosis in SHE cells. The objective of this study was to elucidate the mechanisms of action of zinc on the apoptotic pathway. Effects of 100 and 150 micromol L(-1) ZnCl(2) on the expression of two members of the Bcl-2 family of proteins and on the transcription factor c-Myc in SHE cells was investigated using RT-PCR. No effect on the proto-oncogene c-myc was observed. Up-regulation of bcl-2 expression was found and bax expression was reduced. These changes have been corroborated by immunoblotting. Effects of Zn(2+) on bcl-2/bax ratio were confirmed in apoptotic camptothecin-treated SHE cells. Cloned and sequenced cDNAs obtained from RT-PCR amplifications allowed us to check the RT-PCR products encoded the expected proteins. This study demonstrated that zinc acts in the early phases of the apoptotic process by modification of the bcl-2/bax ratio in normal and apoptotic SHE cells.

Animals↗
PubMed2004

Relationship between two oxidative stress biomarkers, malondialdehyde and 8-oxo-7,8-dihydro-2'-deoxyguanosine, in the freshwater bivalve Unio tumidus.

This study addresses the question of the relation between cellular and genomic oxidative damages in freshwater bivalves in realistic conditions of exposure in the field. Membrane and genomic oxidative damages were studied by means of lipid peroxidation and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), respectively. Malondialdehyde (MDA) was used as an indicator of lipid peroxidation. The biomarkers were measured in the digestive gland and the gills of mussels (Unio tumidus) after 7 and 21 days of exposure in four ponds of the Moselle Basin, during three field studies conducted in 1999 and 2000. Effects measured at three sites (1R, 3C and 4M) were moderate and lipid peroxidation was slightly enhanced in mussels transferred in these ponds. In contrast, an important degradation was observed at site 2V reflected by a sharp increase in MDA and 8-oxodGuo concentrations in 2000. The biomarker responses agreed with the results of physicochemical analyses that indicated a worsening of water quality at the same site. Globally, a relationship was found between MDA increase and 8-oxodGuo formation, in the digestive gland after 7 days of exposure, and later in the gills (21 days). Responses of the digestive glands and gills to the oxidative parameters appeared correlated only after 21 days of exposure. The biomarkers selected confirmed their sensitivity for appraising the water quality of hydrosystems.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Defense systems of benthic invertebrates in response to environmental stressors.

Environmental stress factors may be responsible for biological changes in living species that are able to overcome deleterious effects depending on their detoxifying capacities. Defense systems present in every living species are involved in elimination of reactive chemical species of endogenous or exogenous origin, neutralization of their effects, repair of initial lesions, and compensation of deficient metabolic pathways. Consequently, the performance of defense systems and their inducibility will explain adaptation to environmental disturbances, whereas their alteration will augur toxicity in the exposed species. Several field studies have illustrated the relationships between antioxidants and toxicity in benthic invertebrates in rivers. They highlighted that defense systems may be useful biomarkers in mechanistic studies of ecotoxicity and in the biomonitoring of living species in polluted environments.

Adaptation, Physiological↗
PubMed2003

ZnCl2 induces Syrian hamster embryo (SHE) cell transformation.

In order to test the hypothesis of a relationship between apoptosis and neoplastic transformation, we studied the transforming potency of zinc, known for its antiapoptotic effects. In this study, zinc chloride (100 microM) was shown to induce morphological transformation (MT) in Syrian hamster embryo (SHE) cells. It was also tested in combination with benzo(a)pyrene (BaP), a positive control for carcinogenicity, or fomesafen, a carcinogenic pesticide with hepatic peroxisomal proliferation properties. A co-exposure of the two carcinogens with 100 microM zinc increased cell transformation in SHE cells. These results were in agreement with the theory of a relationship between the inhibition of apoptosis and induction of cell transformation. The cloning efficiency (CE) of SHE cells seeded at clonal density was raised by zinc, fomesafen and furthermore by the mixture of the two chemicals, which could be explained by the antiapoptotic action of zinc and fomesafen on SHE cells. No change in myc and bax expressions was observed in zinc-treated SHE cells.

Animals↗
PubMed2002

Use of RNA arbitrarily primed PCR to identify genomic alterations in the digestive gland of the freshwater bivalve Unio tumidus at a contaminated site.

The technique of RNA arbitrarily primed polymerase chain reaction (RAP-PCR) was developed to detect DNA damage and variations in gene expression in response to exposure to toxic compounds. This approach was tested on the freshwater bivalve Unio tumidus to explore the ability of RAP-PCR to detect effects induced by river sediment contaminated with polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), and metals. In a first step the primer concentration was optimized to obtain reproducible amplifications of both high- and low-molecular-weight products. Optimized conditions allowed us to detect variations corresponding to the loss of PCR products in some animals exposed at the contaminated site compared with the control. Our results for the RAP-PCR approach performed on separate animals in field studies showed that interindividual variations could correspond to DNA damage and/or variations in gene expression.

Animals↗
PubMed2000

Detection of apoptosis induced by topoisomerase inhibitors and serum deprivation in syrian hamster embryo cells.

The sensitivity of normal diploid Syrian hamster embryo (SHE) cells to apoptosis was tested after treatment with the topoisomerase inhibitors camptothecin and etoposide and after serum withdrawal. Programmed cell death (PCD) was identified through morphological, biochemical, and molecular changes and compared with that of HL60 cell line. The results showed that topoisomerase inhibitors, which were shown to be potent PCD inducers in the HL60 cell line, induced a weaker apoptotic response in SHE cells than after growth factor deprivation. In addition, serum-free medium, which rapidly induced apoptosis in SHE cells, did not affect the HL60 cell line. In both cell types, PCD was expressed by condensed chromatin, fragmented nuclei, and DNA laddering on electrophoretic gels, an indisputable sign of apoptosis. In apoptotic HL60 cells, the cleavage of 113-kDa poly(ADP-ribose)polymerase (PARP) resulted in the so-called apoptotic 89-kDa fragment and was associated with increased caspase-3 activity. In apoptotic SHE cells, PARP degraded early but the degradation profile was not characterized by the appearance of an 89-kDa fragment. Moreover, no activation of caspase-3 was noted. ZnCl(2), which is known to prevent protease activity responsible for apoptosis features, inhibited PARP cleavage and nuclear modifications induced by apoptotic stimuli in both cell types, but with a higher sensitivity in SHE cells. Apoptosis induced by serum deprivation was linked with c-myc negative regulation in SHE cells, but not with p53 protein accumulation, while topoisomerase inhibitors led to p53 stabilization without any change in c-myc expression. Serum-free medium and topoisomerase inhibitors did not modify c-myc expression in the HL60 cell line. The overall results demonstrated that apoptosis, which is a carefully regulated process of cell death, may proceed through mechanisms varying according to cell type or apoptosis inducer. In addition, markers which are generally considered hallmarks of apoptosis may fail to appear in some cell types.

Animals↗
PubMed2000

Antioxidant biomarkers in freshwater bivalves, Unio tumidus, in response to different contamination profiles of aquatic sediments.

Antioxidant systems were studied in the freshwater bivalve Unio tumidus transplanted from a control site to four different contaminated areas, in order to study the biological response according to the contamination characteristics. Reduced and oxidized glutathione (GSH, GSSG), the activities of antioxidant enzymes such as selenium-dependent and non-selenium-dependent glutathione peroxidases (SeGPx and non-SeGPx), and glutathione reductase (GRd) were measured in the gills and the digestive gland of the mussels after 15 days of exposure at different sites. Lipid peroxidation (LPO) was evaluated by means of malondialdehyde measurements (MDA). The four sites investigated were located in the valleys of Fensch (F), Moselle (M), Lot et Garonne (LG), and Sarthe (S). At each site, the bivalves were placed upstream (Up) from an identified pollution source (a cokery, a laundry, or a foundry) and downstream (Do), close to the effluent outfall (Do(1)) or farther (Do(2)). The goal was to study the antioxidant response in relation to the pollution gradient. Metals and congeners of PAHs, PCBs, and organochlorinated pesticides were analyzed in the river sediments of each station. The exposure of the bivalves at the most highly polluted sites or close to the pollution source led to a sharp depletion in some antioxidant parameters, namely GRd, SeGPx, and GSH. The decrease in enzyme activities could reach 80% for GRd and 70% for SeGPx, while GSH depletion could yield 70%, leading then in an induction of lipid peroxidation, either in the digestive gland or in the gills. The higher the MDA concentrations, the lower the activity of these three antioxidant parameters, suggesting that they could be biomarkers for toxicity. Yet, a depletion in these parameters was sometimes insufficient for cytotoxicity to be induced, since lipid peroxidation failed to appear in some cases where antioxidant depletion was clear, although not so severe. The response of the gills and the digestive gland was not always paralleled, which can be explained by differences in the bioavailability of pollutants. In some cases, a relationship was not found between the antioxidant response and the degree and the type of contamination in sediments, suggesting that the effects could result from nonidentified pollutants or/and be indicators of bio-availability.

Animals↗
PubMed2000

Comparison of four chronic toxicity tests using algae, bacteria, and invertebrates assessed with sixteen chemicals.

The performances of four chronic toxicity tests, comprising the Daphnia magna 21-day (d) (crustacean), Brachionus calyciflorus 2-d (rotifer), Pseudokirchneriella subcapitata 72-h (green algae), and the Microtox chronic 22-h (bacteria) tests, were compared. Sixteen chemicals with toxicity covering 6 orders of magnitude were studied. Very high correlations were found between the NOEC/EC(10) Pseudokirchneriella 72-h, NOEC/EC(10) Brachionus 2-d, and the NOEC Daphnia 21-d tests. The toxicological response of rotifers and microalgae were within the same order of magnitude as the response of Daphnia in 80% of cases (13/16 chemicals). The Microtox chronic test also anticipated the overall results of the Daphnia 21-d test, but the prediction was rather imprecise, compared with microalgae and rotifers. The test measuring the algal growth inhibition of P. subcapitata after 72h was the most sensitive bioassay. Toxicity on microalgae after 72h could be estimated after 5h by measuring either the direct fluorescence of either photosynthetic pigments or fluorescein diacetate in 56 and 43% of cases, respectively. The median value of the ratio between EC(10) and EC(50) was 3.75, 2, and 1.5 with the algae, the rotifers, and the bacteria, respectively.

Algorithms↗
PubMed2000

PARP degradation in apoptotic Syrian hamster embryo (SHE) cells compared to HL60 cell line.

In this study, we attempted to identify apoptotic Syrian hamster embryo (SHE) cells by detecting the specific cleavage of poly(ADP-ribose)polymerase (PARP). Apoptosis was unequivocally identified in serum-deprived SHE cells. After protein electrophoresis and transfer, the anti-PARP antibody (C-2-10) was applied in order to visualize PARP degradation and the anti-polymer antibody (LP96-10) was used to identify PARP and its expected 89-kDa fragment on the membrane after renaturation and NAD+ addition. Results showed that PARP rapidly disappeared during apoptosis in SHE cells, but the resulting fragment remained undetectable with the anti-PARP antibody and no stable polymerase activity of this fragment was measured using anti-polymer antibody. Serum-starved SHE cells were compared to the etoposide-treated HL60 cell line as a control for typical apoptosis-related PARP cleavage. These results underline the fact that while PARP degradation is a criterion for apoptosis, the diagnosis of apoptosis can not rely exclusively on the appearance of its 89-kDa fragment as this signal may fail to appear in some cell systems.

Animals↗
PubMed1999

Apoptosis inhibition and ornithine decarboxylase superinduction as early epigenetic events in morphological transformation of Syrian hamster embryo cells exposed to 2-methoxyacetaldehyde, a metabolite of 2-methoxyethanol.

We have conducted a study to determine the carcinogenic potential of ethylene glycol monomethyl ether (EGME), a member of the glycol ether family, as compared to its reactive metabolite 2-methoxy-acetaldehyde (MALD). Since disruption of equilibrium between cell proliferation and cell death is thought to play a key role in multistage carcinogenesis, we investigated, in Syrian hamster embryo (SHE) cells exposed to various doses of EGME and MALD, impairment in apoptosis rate and in ornithine decarboxylase (ODC) metabolism. The activity of this rate-limiting enzyme of polyamine biosynthesis is closely related to cell proliferation and cell transformation. At the end-point, comparative action of the two products on SHE cell morphological transformation frequency was evaluated. One-stage exposure of SHE cells to 2 mM EGME and 200 microM MALD for 5 h did not change basal apoptotic level, whereas 0.16 microM phorbol ester (TPA) decreased it. Using two-stage exposure protocol (1 h xenobiotic followed by 5 h TPA), MALD strongly inhibited apoptosis more than did TPA alone; the parent compound EGME did not have any effect on TPA inhibiting action. Western blotting analysis showed that sequential treatment (MALD/TPA) increased Bcl-2 oncoprotein expression, whereas Bcl-XL and Bax proteins were not changed. The same staged exposure of SHE cells to MALD/TPA strongly induced ODC activity, and the rate was higher than that obtained with TPA alone: this was accompanied by an increase of ODC protein level. This ODC superinduction was not observed with EGME/TPA treatment. In long-term SHE-cell morphological transformation assay, staged exposure to MALD (800 microM or 1 mM for 24 h) followed by TPA applications increased the number of transformed colonies at the seventh day. Such early cooperative events as apoptosis inhibition and ODC superinduction, followed by the increase of SHE-cell transformation frequency, are highly indicative of a carcinogenic potential for the metabolite, MALD.

Acetaldehyde↗
PubMed1998

Surgical repair of patellar luxation in llamas: 7 cases (1980-1996).

OBJECTIVE: To evaluate anatomy of the stifle in llamas and determine outcome of llamas that underwent surgery for repair of patellar luxation. DESIGN: Anatomic and retrospective study. ANIMALS: 6 llamas with unilateral patellar luxation and 1 llama with bilateral luxations. PROCEDURE: 6 stifles from llama cadavers were dissected to determine anatomy. Medical records were reviewed to identify history, procedure, outcome, and complications of llamas that underwent surgery. RESULTS: 6 llamas had lateral patellar luxation (including the llama with bilateral luxations), and 1 had medial patellar luxation. Six llamas had a history of trauma before onset of clinical signs. Two llamas underwent tibial tuberosity transposition, but luxation recurred in both and 1 had problems with breakage of implants. The other 5 llamas underwent imbrication and release procedures; however, luxation recurred in 4 of the 5. Surgery was repeated in 2 llamas, with successful outcomes. CLINICAL IMPLICATIONS: Results suggest that imbrication and release procedures may be useful for correction of patellar luxation in llamas without other bony abnormalities. However, long (20 cm) imbrication and release incisions are needed for a successful outcome. Use of a sling after surgery, to allow a gradual return to weight bearing and exercise, may also be important.

Animals↗
PubMed1998

Two-stage exposure of Syrian-hamster-embryo cells to environmental carcinogens: superinduction of ornithine decarboxylase correlates with increase of morphological-transformation frequency.

As part of environmental toxicology, it is important to assess both the carcinogenic potential of xenobiotics and their mode of action on target cells. Since dysregulation of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, is considered as an early and essential component in the process of multistage carcinogenesis, we have studied the mode of ODC induction in Syrian-hamster-embryo(SHE) cells stage-exposed to carcinogens and to non-carcinogens. One-stage (5 hr) treatment of SHE cells with 50 microM clofibrate (CLF), a non-genotoxic carcinogen, or with 0.4 microM benzo(a)pyrene (BaP), a genotoxic carcinogen, slightly decreased basal ODC activity. Using the 2-stage exposure, 1 hr to carcinogen, then replacement by TPA for 5 hr, the ODC activity was higher than that obtained with TPA alone. This ODC superinduction was not observed when SHE cells were similarly pre-treated with non-carcinogenic compounds. Several environmental chemicals, pesticides, solvents, oxidizers and drugs were investigated with this SHE cell model. With one-stage exposure, some xenobiotics decreased basal ODC activity, while for others ODC changes were not noticeable. With 2-stage exposure (chemical followed by TPA), all carcinogens amplified the TPA-inducing effect, resulting in ODC superinduction. Comparative studies of the action of carcinogens and of non-carcinogens, using 2-stage exposure protocols, clearly show a close relationship between ODC induction rate and morphological transformation frequency.

Animals↗
PubMed1998

Effect of aluminum on superoxide dismutase activity in the adult rat brain.

Male rats were treated daily with an intraperitoneal injection of 15 mg aluminum (Al chloride)/kg body weight for 17 d, in order to study the effects on superoxide dismutase (SOD) activities in the brain (cortex). No significant difference between control and treated animals was registered in the Cu/Zn and Mn SOD activities in the gray matter of the cortex. High Al levels were found in the plasma, the spleen, and the liver of the treated animals in comparison to the controls, but not in the cortex homogenates (gray matter). In addition, Al induced a significant decrease in food ingestion and weight gain.

Aluminum Chloride↗